Mitochondria are organelles in eukaryotic cells. They generate most of the cells' supply of adenosine triphosphate (ATP), which is used as an energy source. Thus, mitochondria are indispensable for energy production, for the survival of eukaryotic cells and for correct cellular function. In addition to supplying energy, mitochondria are involved in a number of other processes such as cell signaling, cellular differentiation, cell death as well as the control of the cell cycle and cell growth. In particular, mitochondria are crucial regulators of cell apoptosis and they also play a major role in multiple forms of non-apoptotic cell death such as, e.g., necrosis.
In recent years many papers have been published describing mitochondrial contribution to a variety of diseases. Some diseases may be caused by mutations or deletions in the mitochondrial genome, while others may be caused by damage of the mitochondrial function. At present there is treatment available that can cure mitochondrial diseases.
In view of the recognized importance of maintaining or restoring a normal mitochondrial function, there is a need to identify substances which can be used to protect the mitochondrial structure and function or which can be used to restore or treat dysfunctions in the mitochondria.
Alpha-1-microglobulin (A1M) is a 26 kDa plasma and tissue protein which has been isolated and characterized from plasma, liver and urine from several species including man and plaice (31). In plasma, A1M is found in free form as well as covalently bound to other larger plasma proteins. In humans, A1M forms complexes with IgA, albumin and prothrombin (5). Free A1M and various high-molecular weight complexes are also present in the extracellular matrix of all tissues both originating from plasma as well as from peripheral synthesis (4). In the tissues, A1M is preferentially localized to the interfaces between blood and tissue in blood vessels, air and tissue in the lung, and mother and fetus in placenta, especially at sites of injury (44). The physiological function of A1M is not known, but it has been shown to have reductase activity, and to bind free heme and radicals, suggesting that it may have protective functions during situations with oxidative stress (31). A1M binds to many cell types, in many instances followed by internalization (36, 49).